Research in our laboratory has been directed towards examining the properties of tRNA methyltransferases purified from rat mammary tumors. An N2-guanine methylating activity, purified from DMBA-induced mammary tumors, has been found to differ from the N2-guanine methyltransferases of non-neoplastic mammary tissue in its ability to exhaustively methylate bacterial tRNA. The tumor enzyme also shows a higher molecular weight and places N2-methylguanine on a wider range of tRNAs than the non-tumor enzyme. This project is designed to define the properties of the methyltransferase found in tumors and to explore the relationship between altered methylating activity and tRNA methylation in neoplastic tissues. We propose to 1) compare the structural and functional characteristics of N2-guanine methyltransferases from mammary tumor and normal tissue; 2) study a variety of transplantable tumors for the appearance of this altered guanine methyltransferase and for similar differences in other tRNA methylating enzymes; 3) analyze the modified tRNAs which arise when using tumor or normal methyltransferases to methylate tRNA from normal or neoplastic tissue: and 4) examine the methylation of eucaryotic precursor tRNAs by normal and tumor methyltransferases.